HDL biology
HDL from patients with CETP- or hepatic-lipase-deficiency hyperalphalipoproteinemia is not dysfunctional and shows enhanced cholesterol efflux from macrophages (Atherosclerosis 2014)
Original title: Improved plasma cholesterol efflux capacity from human macrophages in patients with hyperalphalipoproteinemia
Since it remains unclear whether the marked HDL-cholesterol elevation caused by CETP or hepatic lipase (HL) deficiency confers atheroprotection, cholesterol efflux from human THP-1 macrophages to total plasma or isolated HDL subfractions was measured in patients with hyperalphalipoproteinemia (HALP) carrying molecular defects in either the CETP or LIPC gene. HALP was associated with increased plasma cholesterol efflux capacity from macrophages, primarily through stimulation of both SR-BI- and ABCA1-dependent efflux pathways, driven respectively by a quantitative elevation in HDL2 and an enhanced intrinsic capacity of HDL3 subspecies. HDL particles from HALP patients with molecular defects in either CETP or LIPC are therefore not dysfunctional and efficiently stimulate cholesterol efflux from human macrophages.
Original abstract
Objectives: CETP or HL deficiencies lead to a marked increase in HDL-C levels however the atheroprotective effect of this phenotype, in particular the ability of HDL particles to remove cholesterol from human macrophages, remains to be determined.
Methods: We measured cholesterol efflux from human THP-1 macrophages to total plasma or to isolated HDL subfractions in patients with HALP carrying molecular defect in either the CETP or LIPC gene.
Results: We demonstrate that HALP is associated with an increased plasma cholesterol efflux capacity from human macrophages. This observation is primarily related to a stimulation of both SR-BI and ABCA1 dependent efflux pathways as a result of quantitative elevation in HDL2 and enhanced intrinsic capacity of HDL3 subspecies, respectively.
Conclusion: HDL particles from HALP patients with molecular defect within either CETP or LIPC gene are not dysfunctional and are efficient to stimulate cholesterol efflux from human macrophages.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.